The principal objectives of the proposed investigations include: 1) the study of the mechanism of action of environmental olefinic toxins such as vinyl halides (e.g., vinyl chloride, trichloroethylene) and vinyl ethers (e.g., aflatoxin B1), 2) to develop synthetic approaches to the proposed ultimate toxic and/or carcinogenic metabolites of these toxins, and 3) to investigate the possible use of these metabolites (e.g., epoxides of the vinyl halide and the vinyl ether) as synthetic reagents. Unstable and reactive epoxide derivatives of vinyl halides and ethers will be synthesized either by photochemical means or from bromo-hydrin ester derivatives employing controlled conditions. The in vitro reaction of the synthesized epoxides with bio-macromolecules as well as various nucleophiles will be studied with the intent of isolating and characterizing the covalently bound products. Emphasis will be placed on reactions with nucleic acids. The possibilities of reaction with the back-bone phosphate and the cross-linking reaction of these epoxide metabolites will be examined. Elucidation of the structure of the binding product using radioactive olefins in the presence of rat liver microsome will be attempted. The use of these reactive epoxides in organic synthesis will include nucleoside synthesis using the cyclic enol ether epoxide. The proposed investigation would provide pertinent information concerning the mode of action and/or carcinogenic environmental olefins on a molecular basis.